The objective of this shared equipment grant is to obtain a JEOL JEM-1230 transmission electron microscope, a specimen rotation holder, a GATAN Ultrascan 1000 CCD camera, and a dedicated computer, for the community of biomedical investigators at the J. David Gladstone Institutes at the University of California, San Francisco (UCSF). The users of the new equipment have a wide range of NIH-supported biomedical research projects and collectively boast many decades of experience with electron microscopy. Their interests include investigating genetic and acquired defects in the nuclear envelope, exploring the roles of different apolipoprotein E isoforms in neurodegenerative disease, defining the influence of G proteins on the development of cardiomyopathy, and studying the roles of triglyceride-synthesizing genes in the liver and intestine. Currently, the demand for electron microscopy far exceeds our capacity. The new microscope, with its digital imaging capabilities, will greatly accelerate the acquisition of ultrastructural images, making it possible to tackle many more research problems. Moreover, the new instrument, unlike older instruments, is much easier to use, opening the door to use by novices, in addition to professional electron microscopists. The new Electron Microscopy Core Facility will be run by Dr. Stephen G. Young. Day-to-day operations will be supervised by Ms. Jinny Wong, who has 30 years of continuous electron microscopy research experience. Dr. Robert Hamilton (UCSF professor of anatomy), a distinguished electron microscopist, will consult with the Core on technical and organizational issues. Gladstone is committed to the maintenance of the instruments and for providing salary support for the Core staff. The new electron microscope is absolutely critical to the ability of Gladstone investigators to train a new generation of biomedical investigators. Increasingly, the answers to biomedical research problems require a combination of biochemical and ultrastructural approaches. The new electron microscope will make it possible for us to teach our trainees a multidisciplinary approach to biomedical investigation. [unreadable] [unreadable]